Sub-noxious Intravesical Lipopolysaccharide Triggers Bladder Inflammation and Symptom Onset in A Transgenic Autoimmune Cystitis Model: A MAPP Network Animal Study.
Sub-noxious Intravesical Lipopolysaccharide Triggers Bladder Inflammation and Symptom Onset in A Transgenic Autoimmune Cystitis Model: A MAPP Network Animal Study.
复制标题
DOI：
10.1038/s41598-018-24833-x
复制
发表时间：
2018-04-26
影响因子：
4.6
通讯作者：
Luo Y
中科院分区：
文献类型：
--
作者：
Kogan P;Xu S;Wang Y;O'Donnell MA;Lutgendorf SK;Bradley CS;Schrepf A;Kreder KJ;Luo Y
间质性膀胱炎/膀胱疼痛综合征（IC/BPS）患者在暴露于轻微膀胱刺激物（如亚临床细菌感染）后可能会出现症状发作。为了重现这种症状发作，我们膀胱内滴注了亚毒性剂量的致尿病性大肠杆菌。大肠杆菌组分脂多糖（LPS），这是一种转基因自身免疫性膀胱炎模型，在≥10周龄时自发发生膀胱炎症。用磷酸盐缓冲盐水（PBS）或含有亚毒性剂量（1 μg）LPS的PBS膀胱内处理雌性URO-OVA/OT-I小鼠（6周龄）。在治疗后第1、7和14天评价小鼠的膀胱炎、骨盆疼痛和排尿功能障碍。用LPS而不是PBS处理的小鼠发展出早期膀胱炎症，巨噬细胞浸润增加。因此，发炎的膀胱表达促炎细胞因子（IL-1β和IL-6）和疼痛介质（P物质前体）的mRNA水平增加。此外，LPS处理的小鼠表现出骨盆疼痛和排尿功能障碍，如排尿频率增加和膀胱容量减少。这些功能变化持续至测试的第14天。我们的研究结果表明，一个单一的亚毒性剂量的膀胱内LPS触发早期膀胱炎症和症状发作的URO-OVA/OT-I小鼠，IC/BPS症状发作的研究提供了一个有用的模型。
Patients with interstitial cystitis/bladder pain syndrome (IC/BPS) can potentially develop symptom flares after exposure to minor bladder irritants such as subclinical bacterial infection. To reproduce this symptom onset, we intravesically instilled a sub-noxious dose of uropathogenic E. coli component lipopolysaccharide (LPS) in young URO-OVA/OT-I mice, a transgenic autoimmune cystitis model that spontaneously develops bladder inflammation at ≥10 weeks of age. Female URO-OVA/OT-I mice (6-weeks old) were treated intravesically with phosphate-buffered saline (PBS) or PBS containing a sub-noxious dose (1 μg) of LPS. Mice were evaluated for bladder inflammation, pelvic pain, and voiding dysfunction at days 1, 7, and 14 post-treatment. Mice treated with LPS but not PBS developed early bladder inflammation with increased macrophage infiltration. Accordingly, the inflamed bladders expressed increased levels of mRNA for proinflammatory cytokines (IL-1β and IL-6) and pain mediator (substance P precursor). In addition, LPS-treated mice exhibited pelvic pain and voiding dysfunction such as increased urinary frequency and reduced bladder capacity. These functional changes sustained up to day 14 tested. Our results indicate that a single sub-noxious dose of intravesical LPS triggers early bladder inflammation and symptom onset in URO-OVA/OT-I mice, providing a useful model for IC/BPS symptom flare study.
登录
查看更多内容
DOI：
10.1111/iju.12309
发表时间：
2014-04
期刊：
International journal of urology : official journal of the Japanese Urological Association
影响因子：
--
作者：
Rosen JM;Klumpp DJ
通讯作者：
Klumpp DJ
影响因子：
--
作者：
Jerde, TJ;Bjorling, DE;Saban, R
通讯作者：
Saban, R
影响因子：
4.4
作者：
Liu, Wujiang;Evanoff, David P.;Luo, Yi
通讯作者：
Luo, Yi
DOI：
10.1152/ajprenal.00202.2014
发表时间：
2015-01-15
影响因子：
4.2
作者：
Bicer, Fuat;Altuntas, Cengiz Z.;Daneshgari, Firouz
通讯作者：
Daneshgari, Firouz
影响因子：
2.1
作者：
Lai H;Gereau RW 4th;Luo Y;O'Donnell M;Rudick CN;Pontari M;Mullins C;Klumpp DJ
通讯作者：
Klumpp DJ